Postmenopausal osteoporosis is a serious public health concern associated with significant morbidity, mortality, deterioration of quality of life, and high health care costs (Kanis J A. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report, WHO Study Group. Osteoporosis Int. 1994; 4:368-8).
Current FDA-approved therapies include anti-resorptive (e.g., bisphosphonate and denosumab) and anabolic (e.g., teriparatide) agents (America's bone health: the state of osteoporosis and low bone mass in our nation, NOF 2002 [NOF 2002]).
While denosumab is relatively new and unstudied, bisphosphonate and teriparatide therapies have contributed to a documented decrease in fracture risk among treated patients (Freemantle N, Cooper C, Diez-Perez A, Gitlin M, Radcliffe H, Shepherd S, et al, Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis, Osteoporosis Int. 2013; 24:209-17).
However, the potentially undesirable side effects associated with these pharmacological therapies, including atypical fractures, osteonecrosis of the jaw, gastro-oesophageal adverse events, and dizziness, along with poor compliance and cost concerns for teriparatide, continue to challenge their overall efficacy [4, 5] (Stroup J, Kane M P, Abu-Baker A M, Teriparatide in the treatment of osteoporosis, Am J Health Syst Pharm 2008; 65:532-9); (Curtis J R, Cai Q, Wade S W, Stolshek B S, Adams J L, Balasubramanian A, et al., Osteoporosis medication adherence: physician perceptions vs patients utilization, Bone 2013; 55:1-6.).
Thus, research efforts are directed towards discovering more effective, lower-cost therapeutic strategies, including natural alternatives with minimal side effects and fewer compliance challenges.
There is growing evidence that oxidative stress, induced by reactive oxygen species (ROS) that increase with aging or with the onset of an inflammatory state, can adversely affect bone homeostasis (Callaway D A, Jiang J X, Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone disease, J Bone Miner Metab 2015; DOI 10.1007/s00774-015-0656-4).
Recent studies have suggested that postmenopausal bone loss may be caused by ROS, which induce a more oxidized bone microenvironment (Maggio D, Barabani M, Pierandrei M, Polidori M C, Catani M, Mecocci P, et al., Marked decrease in plasma antioxidants in aged osteoporotic women: Results of a cross-sectional study, J Clint Endocrinol Metab 2003; 88:1523-7).
An excess of ROS may inhibit osteoblast differentiation and proliferation (Li M, Zhao L, Liu A L, Zeng W S, Luo S Q, et al., Hydrogen peroxide induces G2 cell cycle arrest and inhibit cell proliferation in osteoblast, Anat Res 2009; 292:1107-13).
ROS generated in the extra- or intra-osteoclasts act as signals to enhance osteoclastic differentiation, resulting in more bone resorption (Fraser J H E, Halfrich M H, Wallace W M, Ralston S H., Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvaria, Bone 1996; 19:223-6); (Lee N K, Choi Y G, Baik J Y, Han S Y, Jeong Bae Y S, et al., A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation, Blood 2005; 106:852-9).
Thus, an imbalance in ROS levels can accelerate bone resorption, resulting in bone fragility and fracture: accordingly, eliminating excessive ROS is an effective approach for maintaining bone integrity (Banifi G, Iorio E L, Corsi M M., Oxidative stress, free radical and bone remodeling, Clin Chem Lab Med 2008; 46:1550-5).
Estrogen deficiency, an independent risk factor for bone fragility (Weitzmann M N, Pacifici R., estrogen deficiency and bone loss: an inflammatory state, J Clin Invest 2006; 116:1186-94), has been linked to an increase in oxidative stress.
Dietary supplementation or treatment with antioxidants is an effective approach to counteract and ameliorate excessive ROS production. Lycopene, a carotenoid found in red fruits and vegetables, especially tomatoes and tomato products, is one of the most potent antioxidants but has low oral bioavailability with consequent low efficiency of utilization.